Spastin Interacts With the Centrosomal Protein NA14, and Is Enriched in the Spindle Pole, the Midbody and the Distal Axon

Hum Mol Genet. 2004 Sep 15;13(18):2121-32. doi: 10.1093/hmg/ddh223. Epub 2004 Jul 21.


Hereditary spastic paraplegia (HSP) is characterized by the specific retrograde degeneration of the longest axons in the central nervous system, the corticospinal tracts. The gene most frequently involved in autosomal dominant cases of this disease, SPG4, encodes spastin, an ATPase belonging to the AAA family. AAA proteins are thought to exert their function by the energy-dependent rearrangement of protein complexes. The composite function of these proteins is directed by their binding to regulatory factors and adaptor proteins that target their activity into specific pathways in vivo. We previously found that overexpressed spastin interacts dynamically with microtubules and displays microtubule-severing activity. Here, we demonstrate that spastin is enriched in cell regions containing dynamic microtubules. During cell division spastin is found in the spindle pole, the central spindle and the midbody, whereas in immortalized motoneurons it is enriched in the distal axon and the branching points. Furthermore, spastin interacts with the centrosomal protein NA14, and co-fractionates with gamma-tubulin, a centrosomal marker. Deletion of the region required for binding to NA14 disrupts spastin interaction with microtubules, suggesting that NA14 may be an important adaptor to target spastin activity at the centrosome. These data strongly argue that spastin plays a role in cytoskeletal rearrangements and dynamics, and provide an attractive explanation for the degeneration of motor axons in HSP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases
  • Autoantigens / analysis
  • Autoantigens / metabolism*
  • Axons / chemistry*
  • Calcium-Binding Proteins / analysis*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Extracts / immunology
  • Cell Nucleus / immunology
  • Cell Nucleus / metabolism
  • Centrosome / immunology
  • Centrosome / metabolism
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Microtubules / metabolism
  • Motor Neurons / immunology
  • Motor Neurons / metabolism
  • Nuclear Proteins / analysis
  • Nuclear Proteins / metabolism*
  • Sequence Deletion
  • Spastic Paraplegia, Hereditary / metabolism
  • Spastin
  • Spindle Apparatus / chemistry*
  • Spindle Apparatus / metabolism
  • Tubulin / analysis
  • Tubulin / metabolism
  • Two-Hybrid System Techniques


  • Autoantigens
  • Calcium-Binding Proteins
  • Cell Extracts
  • NA14 nuclear autoantigen
  • Nuclear Proteins
  • Tubulin
  • Adenosine Triphosphatases
  • Spastin
  • SPAST protein, human